Transthoracic drug delivery device

ABSTRACT

The present invention provides a transthoracic drug delivery device that utilizes pressure to determine the precise location of the distal tip of the delivery tube of the device to insure that therapeutic substances are ejected into the myocardium and not dissipated in unintended tissue locations. In one embodiment the drug delivery device comprises a pressure sensing tube mounted in parallel to a drug delivery tube wherein the tubes are staggered so that the pressure tube extends beyond the delivery tube. When the myocardium is penetrated by the tubes, advancement into the heart and penetration into the left ventricle by the pressures sensing tube results in a pressure increase that indicates to the physician that the drug delivery tube, by its placement relative to the pressure sensing tube is still in the myocardium and, thus, prepared to deliver the drug. In another embodiment, a steerable syringe is provided so that multiple sites in the myocardium can be treated with a therapeutic substance with only one penetration into the heart. Once the delivery tube of the syringe penetrates the left ventricle, its distal tip can be deflected back toward the endocardial surface and the tube withdrawn proximally to cause penetration of the tip into the myocardium. A pressure sensor mounted to the tube indicates, by a measured drop in pressure that the myocardium has been penetrated. The therapeutic substance is ejected into the myocardium and the device is then backed out of the tissue by advancing the syringe in a distal direction. The deflectable tip can be adjusted to a different deflection angle and the delivery tube rotated to make available a circular array of points that may be accessed by the syringe.

RELATED APPLICATION

This application is a divisional of application Ser. No. 09/164,164filed Sep. 30, 1998, now U.S. Pat. No. 6,251,079, issued Jun. 26, 2001.

FIELD OF THE INVENTION

The present invention relates to a device and method for delivering atherapeutic substance to the myocardium of a human heart.

BACKGROUND OF THE INVENTION

Tissue becomes ischemic when it is deprived of adequate blood flow.Ischemia causes pain in the area of the affected tissue and, in the caseof muscle tissue, can interrupt muscular function. Left untreated,ischemic tissue can become infarcted and permanently non-functioning.Ischemia can be caused by a blockage in the vascular system thatprohibits oxygenated blood from reaching the affected tissue area.However, ischemic tissue can be revived to function normally despite thedeprivation of oxygenated blood because ischemic tissue can remain in ahibernating state, preserving its viability for some time. Restoringblood flow to the ischemic region serves to revive the ischemic tissue.

Although ischemia can occur in various regions of the body, often tissueof the heart, the myocardium, is affected by ischemia due to coronaryartery disease, occlusion of the coronary arteries, which otherwiseprovide blood to the myocardium. Muscle tissue affected by ischemia cancause pain and lead to infarction of the tissue. Ischemia can betreated, if a tissue has remained viable despite the deprivation ofoxygenated blood, by restoring blood flow to the affected tissue.

Treatment of myocardial ischemia has been addressed by severaltechniques designed to restore blood supply to the affected region.Coronary artery bypass grafting (CABG) involves grafting a venoussegment between the aorta and the coronary artery to bypass the occludedportion of the artery. Once blood flow is redirected to the portion ofthe coronary artery beyond the occlusion, the supply of oxygenated bloodis restored to the area of ischemic tissue.

Early researchers, more than thirty years ago, reported promisingresults for revascularizing the myocardium by piercing the muscle tocreate multiple channels for blood flow. Sen, P. K. et al.,“Transmyocardial Acupuncture—A New Approach to MyocardialRevascularization”, Journal of Thoracic and Cardiovascular Surgery, Vol.50, No. 2, August 1965, pp. 181-189. Although others have reportedvarying degrees of success with various methods of piercing themyocardium to restore blood flow to the muscle, many have faced commonproblems such as closure of the created channels. Various techniques ofperforating the muscle tissue to avoid closure have been reported byresearchers. These techniques include piercing with a solid sharp tipwire, hypodermic tube and physically stretching the channel after itsformation. Reportedly, many of these methods still produced trauma andtearing of the tissue that ultimately led to closure of the channel.

An alternative method of creating channels that potentially avoids theproblem of closure involves the use of laser technology. Researchershave reported success in maintaining patent channels in the myocardiumby forming the channels with the heat energy of a laser. Mirhoseini, M.et al., “Revascularization of the Heart by Laser”, Journal ofMicrosurgery, Vol. 2, No. 4, June 1981, pp. 253-260. The laser was saidto form channels in the tissue that were clean and made without tearingand trauma, suggesting that scarring does not occur and the channels areless likely to experience the closure that results from healing. U.S.Pat. No. 5,769,843 (Abela et al.) discloses creating laser-made TMRchannels utilizing a catheter based system. Abela also discloses amagnetic navigation system to guide the catheter to the desired positionwithin the heart. Aita U.S. Pat. Nos. 5,380,316, and 5,389,096 discloseanother approach to a catheter based system for TMR.

Although there has been some published recognition of the desirabilityof performing transmyocardial revascularization (TMR) in a non-lasercatheterization procedure, there does not appear to be evidence thatsuch procedures have been put into practice. For example, U.S. Pat. No.5,429,144 Wilk discloses inserting an expandable implant within apreformed channel created within the myocardium for the purposes ofcreating blood flow into the tissue from the left ventricle.

Performing TMR by placing stents in the myocardium is also disclosed inU.S. Pat. No. 5,810,836 (Hussein et al.). The Hussein patent disclosesseveral stent embodiments that are delivered through the epicardium ofthe heart, into the myocardium and positioned to be open to the leftventricle. The stents are intended to maintain an open channel in themyocardium through which blood enters from the ventricle and perfusesinto the myocardium.

Angiogenesis, the growth of new blood vessels in tissue, has been thesubject of increased study in recent years. Such blood vessel growthprovides new supplies of oxygenated blood to a region of tissue that hasthe potential to remedy a variety of tissue and muscular ailments,particularly ischemia. Primarily, the study has focused on perfectingangiogenic factors such as human growth factors produced from geneticengineering techniques. It has been reported that injection of such agrowth factor into myocardial tissue initiates angiogenesis at thatsite, which is exhibited by a new dense capillary network within thetissue. Schumacher et al., “Induction of Neo-Angiogenesis in IschemicMyocardium by Human Growth Factors”, Circulation, 1998; 97:645-650. Theauthors noted that such treatment could be an approach to management ofdiffused coronary heart disease after alternative methods ofadministration have been developed.

Mechanical devices have been disclosed for delivering therapeuticsubstances to the myocardium. International patent publication no. WO98/05307 by Local Med, Inc. discloses a method of using a conventional,rigid syringe and needle to access the myocardium and left ventricle todeliver a therapeutic substance such as an angiogenic factor.

SUMMARY OF THE INVENTION

The present invention provides a transthoracic drug delivery device thatis specially configured to be precisely located in the myocardium foraccurate placement of a therapeutic substance such as a drug. The devicecomprises a syringe having a delivery tube that is capable ofpenetrating the myocardium via the epicardium to access the leftventricle. Access to the heart is gained through the thorax. A pressuremonitor associated with the device indicates the position of the distaltip of the delivery tube. It is noted that, throughout the discussion ofthe invention in the specification, “distal” is meant to indicate thedirection along the access path of the device leading internal to thepatient and “proximal” indicates the direction along the access pathleading external to the patient. Pressure may be monitored through thedelivery tube or through a separate pressure tube associated with thedelivery tube. Specifically, the amount of pressure measured through thetube of the device informs the physician whether the distal port of thetube has penetrated the myocardium completely to reach the leftventricle. In the case of separate delivery and pressure tubes, thedistance between the pressure tube opening and drug delivery tubeopening is known, so the user can determine whether the drug deliverytube opening is still within the myocardium, and, therefore,appropriately placed to inject a drug into the myocardium. Multiple drugdelivery tubes may be associated with the device to perfuse the drugmore quickly through multiple ports into the myocardium. It is notedthat throughout the specification “drug” includes all varieties oftherapeutic substances that may be beneficial to the body, includingpharmaceutical agents, genetically engineered substances or naturalsubstances.

In another embodiment, a pressure sensing hypodermic tube, as in thefirst embodiment, is used to transthoracically access the heart andpenetrate the left ventricle. However, the second embodiment iscomprised of a single pressure sensing tube. The distal portion of thepressure tube is flexible and made controllable or steerable bymechanisms well known in the art of catheter manufacture such as a pullwire bonded to the distal end of the tube and extending proximally formanipulation outside the patient. After penetrating the left ventricle,the single pressure tube may be bent into a “J” configuration and theshaft withdrawn proximally to cause the curved tip of the J portion topenetrate the myocardium again, through the endocardial surface whilemoving in a proximal direction, similar to a fish hook. Entrance of thedistal port of the pressure tube into the tissue results in a drop ofmeasured pressure, indicating to the user that the distal tip of thepressure tube is within tissue, and, thus, appropriately placed toinject the drug or therapeutic substance being carried by the device.

After delivery of the therapeutic substance to a first location, thedistal tip of the pressure tube may be backed out of the tissue bydistal movement of the device into the ventricle and another locationaccessed. The steerable distal tip of the device permits the distal tipto be deflected through various angles relative to the longitudinal axisof the tube. Combining this range of movement with the rotationalcapability inherent in the device provides a locus of points about thepenetration point into the ventricle where the distal tip of the needlecan be placed into the myocardium to delivery therapeutic substances.

It is an object of the present invention to provide a drug deliverydevice that can access the myocardium and left ventricle of the hearttransthoracically and accurately indicate the position of the distal tipof the device within the heart.

It is another object of the invention to provide a drug delivery devicethat is capable of delivering a therapeutic substance to the myocardiumof the heart accurately and easily.

It is yet another object of the invention to provide a drug deliverydevice that is capable of delivering a therapeutic substance to themyocardium of the heart quickly via a plurality of delivery conduits.

It is yet another object of the invention to provide a drug deliverydevice that is capable of reaching a plurality of delivery locations inthe myocardium with a single access to the heart.

It is yet another object of the invention to provide a drug deliverydevice for placement within the heart that is associated with a pressuresensor having adequate sensitivity to discern whether the pressuresensor port is within the myocardium or within the left ventricle.

It is yet another object of the invention to provide a delivery devicethat is configured to have a deflectable tip so that the reverse side oftissue having been accessed by the device can also be penetrated by thesharp tip of the device as the device is moved back along its accesspath.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects and advantages of the invention will beappreciated more fully from the following further description thereof,with reference to the accompanying diagrammatic drawings wherein:

FIG. 1 is a diagrammatic, sectional illustration of the left ventricleof the human heart having the drug delivery device of the presentinvention inserted through the myocardial tissue;

FIG. 2 is a detailed sectional illustration of a portion of myocardialtissue that has been penetrated by the drug delivery device of thepresent invention;

FIG. 3 is a detailed sectional illustration of a portion of myocardialtissue that has been penetrated by an alternate embodiment of the drugdelivery device of the present invention;

FIG. 4 is a diagrammatic, sectional illustration of the left ventricleof the human heart wherein the myocardium has been penetrated by asecond embodiment of the drug delivery device; and

FIGS. 5-8 show a series of detailed sectional illustrations of a portionof the myocardium having been penetrated by the second embodiment of thedelivery device.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENT

FIG. 1 shows a sectional view of the left ventricle of the heart 1having been penetrated by the drug delivery device of the presentinvention. The multiple tube embodiment 10 is comprised of a pressuretube 12 for monitoring pressure and a delivery tube 14 for dispensingthe therapeutic substance or drug into the myocardium 4. The tubes maycomprise metal hypodermic tubing or any tubing capable of beingconfigured to have sufficient strength and sharpness to penetratetissue. The tubes are joined together side-by-side in parallelrelationship, but are offset so that the pressure tube extends beyondthe delivery tube. Both the pressure tube 12 and delivery tube 14 havesharpened distal tips 16 and 18 and open distal ports 20 and 22,respectively. The device is delivered through the thorax and epicardialsurface 8 of the heart and advanced through the myocardium 4 until thepressure tube 12 penetrates the left ventricle 2. Alternatively, as willbe described in further detail below, the tubes may be formed fromrelatively flexible material having rigid sharp inserts at the distalends and the flexible tubes being temporarily fortified to resistbuckling during delivery by an inner stiffening element that may bewithdrawn after delivery.

The proximal end 26 of the delivery tube 14 is joined to a pressurizedsource of a therapeutic substance 27 such as may be provided by asyringe (not shown). The pressure tube is joined at its proximal end 24to a pressure monitor 25 for measuring the pressure sensed at thepressure tube distal port 20. As the pressure tube is inserted throughthe tissue of the heart, measured pressure will be low; however, oncethe pressure port 20 reaches the left ventricle 2, measured pressureincreases dramatically signaling the physician that the ventricle hasbeen reached.

The distance D between the relative longitudinal spacing of the pressuretube and delivery tube (measured from distal tip 16 to distal tip 18) isknown. Therefore, at the moment during advancement of the device intothe heart when pressure dramatically increases, not only is the positionof distal tip 16 known (having penetrated the endocardial surface 6 toaccess the ventricle 2) but also, the position of the delivery tubedistal tip 18 will be known relative to the endocardial surface 6.Therefore, if it is desired to deliver a therapeutic substance to acertain depth beneath the endocardial surface 6 of the myocardium 4, thepressure and delivery tubes 12 and 16 can be arranged relative to eachother to provide that distance D between their distal tips 16 and 18.Upon penetration of the ventricle, the therapeutic substance can bedischarged from the delivery port 22 at the desired distance beneath theendocardial surface 6. During this procedure, the pressure tube 12 mayalso be used to inject contrast media into the ventricle to helpvisualize the position of the device. FIG. 3 shows a variation of themultiple tube embodiment employing a plurality of delivery tubes, eachspaced a distance beneath the distal tip of the pressure tube 12. Thepurpose of multiple delivery tubes is to provide increased drug deliverycapability to surrounding myocardial tissue 4 with each penetration ofthe device into the heart.

The second embodiment of the drug delivery device further addresses thedesirability of minimizing the number of times that the device must beinserted into the heart. A deflectable syringe tube 28 is shown in FIG.4 protruding through the myocardium 4 into the left ventricle 2 of ahuman heart 1. After penetrating the myocardium, the distal portion 30of the tube 28 may be deflected away from the longitudinal axis of thetube by as much as approximately 180°. The objective of providing such alarge deflection is to permit the distal tip 32 of the tube to penetratethe endocardial surface 6 as the tube is withdrawn in a proximaldirection from the ventricle 2. In the deflected configuration, thedistal portion 30 of the tube is J-shaped and, therefore, pierces thetissue in similar fashion to a fishhook as it is withdrawn proximally.Once the distal port 34 has penetrated the myocardium, the therapeuticsubstance can be ejected through the port and into the tissue. Theprimary benefit provided by the deflectable tip tube is that multipletissue locations can be reached with a single insertion penetration ofthe device into the heart.

As shown in FIG. 5, the tube should be inserted into the myocardium 4while in a straight configuration. However, to be deflectable, at leastthe distal portion 30 of the tube must be flexible. Therefore, toprovide sufficient longitudinal support during delivery through theheart tissue, a stiffening element 36 such as a stainless steel wire,may be advanced through the lumen 38 of the tube, extending to thedistal tip 32. At least the distal portion 30 of the tube should befabricated from a relatively flexible material, such as a relatively lowdensity polymer, to provide adequate flexibility for bending when thetip is deflected. The distal tip 32 may comprise an insert of a morerigid material bonded to the flexible material, such as a high densitypolymer or stainless steel to provide a sharp, piercing profile.

As shown in FIG. 6, after penetrating the myocardium 4, the stiffeningelement 36 is withdrawn proximally somewhat from the distal portion 30of the tube 28 so that the tip 32 may be deflected to present itspiercing distal tip 32 toward the endocardial surface 6 of themyocardium 4. The stiffening element 36 may, but need not be withdrawncompletely from the tube to deflect the tip. The tip deflection may beactuated by a pull wire extending through the tube 28 and joined to thearea of the distal tip 32. The pull wire extends proximally, out of thedevice so that it may be manipulated by the physician external to thepatient. Pulling the pull wire puts tension on one side of the tubewhich tends to cause the flexible distal portion 30 to curve in thedirection that the tension is being applied. Such pull wire arrangementsare well known in the catheter art and are not discussed in detail here.

As shown in FIG. 7, the deflected tip is drawn proximally into theendocardial surface 6. In this configuration, the therapeutic substanceis ejected from the port 34 into the tissue 4. After the desiredquantity of therapeutic substance has been delivered to the location,the distal tip 32 is withdrawn from the myocardium 4 by moving the tube28 distally slightly. The lumen of the tube 34 is in communication witha pressure monitor as was described in connection with the previousembodiment. Pressure sensing is useful in the present embodiment so thatthe physician can determine when the distal tip 32 of the tube haspenetrated the myocardium 4 so that drugs can be delivered through port34. In use, the pressure monitor indicates a high pressure when the port32 is open to the ventricle. However, the pressure reading dropsappreciably once the distal port 34 has become submerged within tissueindicating to the user that the distal tip is implanted.

As shown in FIG. 8, the withdrawn distal tip 32 and distal portion 30may be adjusted to locate a new tissue site in the myocardium todelivery the therapeutic substance. The amount of deflection of thedistal tip, represented by arrow 40 may be adjusted to reach a newlocation within the myocardium 4 into which a therapeutic substanceneeds to be delivered. Additionally, the tube 28 may be rotated, asindicated by arrow 46 to provide a circle of points that are accessibleby the deflectable tip tube. A possible new position for the distalportion 30 of the tube is shown in phantom in FIG. 8 to exhibit thesteering capabilities of the device.

From the foregoing it will be appreciated that the invention provides adrug delivery device and method for delivering therapeutic substances tothe myocardium quickly and accurately by accessing the thorax with asyringe and delivery tube device. Additionally, the present inventionprovides a device and method for accessing multiple points on theendocardial surface of the myocardium with a single penetration into theheart.

It should be understood, however, that the foregoing description of theinvention is intended merely to be illustrative thereof and that othermodifications, embodiments and equivalents may be apparent to thoseskilled in the art without departing from its spirit. Having thusdescribed the invention, what we desire to claim and secure by LettersPatent is:
 1. A method of delivering a therapeutic substance to aplurality of sites in the myocardium with a single penetration into theheart comprising: introducing a tube having a deflectable distal portionand distal tip into the left ventricle of the heart; deflecting thedistal tip of the tube so that the tip faces the endocardium; moving thetube in a proximal direction so that the distal tip penetrates theendocardium; ejecting a therapeutic substance through the tube into themyocardium; moving the distal tip from the myocardium by advancing thetube distally; adjusting the position of the tip by changing thedeflection angle of the tip or by rotating the tube to a new myocardiallocation; moving the tube in a proximal direction to insert the distaltip into the myocardium at the new location; ejecting a therapeuticsubstance from the tube into the myocardium.
 2. A method of delivering atherapeutic substance to a plurality of locations within a myocardium asdefined in claim 1 wherein the tube is equipped with a pressure sensorand the presence of the distal tip within myocardial tissue isdetermined by the change in pressure between the pressure indicated whenthe distal tip is in the myocardium versus the pressure indicated whenthe distal tip was in the ventricle.
 3. A method of delivering atherapeutic substance to a plurality of locations within the myocardiumas defined in claim 1 wherein the tube further comprises a stiffeningelement slidable within the tube and prior to introducing the tube,advancing the stiffening element at least through the deflectable distalportion of the tube to provide support while introducing the tube intothe heart and then withdrawing the stiffening element proximal to thedeflectable distal portion prior to deflecting the distal tip of thetube.
 4. A method of delivering a therapeutic substance to a pluralityof sites in the myocardium as defined in claim 1 wherein the tube isintroduced through the epicardium of the heart to reach the leftventricle.